Effect of central muscle relaxants on single-dose pharmacokinetics of peroral paracetamol in man.
Paracetamol (acetaminophen) at a single, 160-450 mg dose was given perorally in combination with central muscle relaxants (CMRs) carisoprodol (200 mg), chlormezanone (100 mg) or orphenadrine (35 mg) in a double-blind, randomized, cross-over study in 10 healthy volunteers. The pharmacokinetic parameters of paracetamol remained unaltered in the presence of the CMRs as compared with those observed after paracetamol without additives, in spite of nearly twenty-fold differences in the dissolution rate between the products. Paracetamol is absorbed mostly in the duodenum, and therefore there is enough time for even the slowly dissolving tablets to release the active principle before the gastric contents are transferred to the area of paracetamol absorption. Some CMRs are anticholinergic compounds and may affect intestinal motility. Our results show, however, that CMRs do not significantly alter the pharmacokinetics of paracetamol, and presumably the antipyretic or analgetic efficacy of paracetamol is not impaired when combination formulations of paracetamol and CMRs are used.
Saano
V
V
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Elo
H A
HA
Paronen
P
P
D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D002626:Chemistry, Pharmaceutical; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D009125:Muscle Relaxants, Central / Q000009:adverse effects / Q000494:pharmacology*; D011897:Random Allocation; D012995:Solubility
D009125:Muscle Relaxants, Central; D000082:Acetaminophen